This proposal is based, in part, on results of a clinical survey indicating a significant prevalence of fluorosis among children occurs in areas having non-fluoridated drinking water. The source of ingested F is not known. This proposal is directed at the possibility that fluoride is derived from the ingestion of discrete, high doses of fluoride, possibly obtained from fluoride tablets, or fluoridated tooth paste. It is very likely that the effects of such acute fluoride doses differ markedly from the chronic effects observed in areas of high fluoride concentrations in drinking water. We observed that enamel deposition follows a circadian rhythm resulting in formation of enamel of two different densities. It is very likely that there are two kinds of secretory ameloblasts, or two secretory cell cycles. This is an important finding pertaining to the basic mechanism of enamel formation. Rhythmic tooth formation has been observed in rat incisors as stripes on the tooth surface and in human enamel as incremental lines. In rats the cyclinical enamel deposition is accentuated by administration of fluoride. The purposes are to examine in detail the hypermineralized and the hypomineralized phases of the secretory, maturation, and erupted regions of the tooth with respect to: (a) the ultrastructure of enamel and enamel matrix; (b) the length of time during which each is predominant; and (c) the cytostructure of the ameloblasts secreting each phase. Secondly, to examine and measure several parameters, including fluoride serum concentrations resulting from ingesting acute fluoride doses. The goal is to investigate the mechanism causing fluorosis in order to better define optimal fluoride treatment for maximal protection without adverse effects on enamel. Thirdly, to determine whether the effect of acute fluoride doses superimposed on ambient fluoride is additive, or, as proposed here, that critical concentrations of ambient fluoride reduce or prevent fluorosis.